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Biomedical subjects

S Hellman

Publications and source records attributed to S Hellman.

At least 163 records · Page 9Linked to original sources
PubMed1980

Evidence for structured variation in self-renewal capacity within long-term bone marrow cultures.

Bone marrow pluripotent stem cells (CFUs) demonstrate capacity for both proliferation and differentiation. The proliferative capacity of CFUs has been measured by serial transplantability and by the Rs, a measurement of CFU production in a single 14-day transfer. In the present study, the self-renewal capacity fo both adherent and nonadherent CFUs from long-term bone marrow cultures was measured. Culture conditions were established such that nonadherent cells were derived from the adherent cell layer. Both adherent and non-adherent cells produced spleen colonies, demonstrating that significant proliferative potential was present in both locations; however, at all times in culture, the CFUs within the adherent stromal cell layer had a significantly greater self-renewal capacity than did the nonadherent CFUs. During the initial establishment of the cultures, the self-renewal capacity of the adherent CFUs decreased as the total number of CFUs per flask increased. After 3 weeks in culture, the self-renewal potential of the adherent CFUs stabilized and was maintained. These results suggest two different mechanisms of stem cell proliferation. In order to increase the most primitive stem cell pool size, there was initial proliferation of early stem cells with a concomitant decrease in self renewal capacity. Once this pool was established, the self-renewal capacity of the adherent CFUs maintained for 13 weeks in culture suggests that CFU production and cell maintenance were achieved by clonal succession.

Animals↗
PubMed1980

Anatomic substages of stage III-A Hodgkin's disease. A collaborative study.

The clinical significance of anatomic substage was assessed in 130 patients with Hodgkin's disease in pathologic stage III-A: stage III1-A includes involvement of spleen, or splenic, celiac, or portal nodes, or any combination of these; stage III2-A includes involvement of para-aortic, iliac, or mesenteric nodes, with or without upper abdominal involvement. Median follow-up was 58 months. Both 5-year disease-free survival, 74% versus 46%, and 5-year survival, 94% versus 65%, were better (P less than 0.001) in stage III1-A than in stage III2-A. In stage III1-A, 5-year disease-free survival was better in patients receiving radiotherapy and chemotherapy than in patients receiving radiotherapy alone as initial treatment, 96% versus 63%, P less than 0.003; however, 5-year survival rates in P = 0.22. For stage III2-A, both 5-year disease-free survival, 76% versus 32%, P less than 0.001, and 5-year survival, 84% versus 56%, P less than 0.03, were superior with radiotherapy-chemotherapy. Consideration of anatomic substage may aid therapeutic planning for stage III Hodgkin's disease.

Hodgkin Disease↗
PubMed1980

Improving the therapeutic index in breast cancer treatment: the Richard and Hinda Rosenthal Foundation Award lecture.

Improving the relationship between desired and undesired effects of therapy, the therapeutic index, is a major goal of cancer therapy. Clinical research pertinent to breast cancer treatment attempting to manipulate this therapeutic index is not restricted to studies in patients. Described herein is research in humans, mouse, machine, marrow, and molecule, concerned with either increasing care or decreasing treatment complications. Molecular studies use 125I-tamoxifen as a specific cytotoxic agent for cells which contain estrogen receptors able to bind the agent and transport it into the nucleus where the limited range radiations are cytotoxic. Murine bone marrow stem cells are heterogeneous as regards their self-renewal potential. Chemotherapeutic agents used in the adjuvant treatment of breast cancer have different effects on these cells. L-Phenylalanine mustard is toxic to the most primitive stem cells and produces a permanent stem cell self-renewal deficit when given to mice in an "adjuvant" setting. Cyclophosphamide and 5-fluorouracil act primarily on later stem cells and do not produce such proliferative limitations. Eliminating breast cancer while preserving normal structure and function is the goal of combining radiation therapy and tumor excision. Results with this technique are comparable to those following mastectomy without loss of the breast or chest musculature.

Animals↗
PubMed1979

Nature of the hemopoietic stem cell compartment and its proliferative potential.

The nature of the hemopoietic stem cell compartment has been the subject of much controversy. Data are presented to support the concept of a 'continuum' model of the stem cell compartment. The important characteristics of this model are that within the continuum there are cells with varying proliferative capacities. As cells move through the compartment, their proliferative capacity becomes more limited, their likelihood to be in cycle increases, and their commitment to a specific differentiated pathway increases. Experiments with busulfan, cyclophosphamide, 5-flurouracil, and BCNU demonstrate defects in proliferative potential of the surviving CFU-S population. These defects persist throughout the life of the animal without any evidence of recovery. The clinical implications of late stem cell failure may be important as a consideration in the use of cytotoxic agents.

Animals↗
PubMed1979

Results of treating stage III carcinoma of the breast by primary radiation therapy.

One hundred sixteen patients with stage III carcinoma of the breast were treated by primary radiation therapy. The 5-year actuarial survival and relapse-free survival were 25% and 22%, respectively. The 5-year actuarial probability of local tumor control for the entire group was 64%. In patients undergoing an excisional biopsy and an interstitial implant of the primary tumor area, local control was 100%. In patients who had either an excisional biopsy or an implant, the 5-year actuarial probability of local control was 77% and 76%, respectively. In contrast, in patients having neither an excisional biopsy nor an implant, local control was only 41%. In patients receiving a total dose of greater than 6000 rad, from external beam treatment or from external beam plus an interstitial implant, the local control was 78% compared to 39% in patients receiving a total dose of less than 6000 rad. Forty-one patients received some form of adjuvant therapy. Both local control and relapse-free survival were improved in patients receiving chemotherapy as the sole adjuvant and in patients receiving chemotherapy combined with an endocrine ablative procedure. However, patients treated with only an endocrine ablative procedure had no improvement in survival nor in local control. These results indicate that primary radiation therapy can provide local control in a high proportion of patients with stage III carcinoma of the breast and suggest that chemotherapy is effective in improving both local control and survival in these patients.

Adult↗
PubMed1979

Results of total body irradiation in the treatment of advanced non-Hodgkin's lymphomas.

Total body irradiation (TBI) was used as primary therapy for 58 previously untreated patients with Stage III or IV non-Hodgkin's lymphoma (NHL). 150 rad was administered, with 15 rad fractions twice a week, with careful monitoring of hematologic status. Thrombocytopenia was the most frequent complication, which resolved in all except 4 patients. Survival at 8 years was 52%, with 14% relapse-free survival. Patients with nodular histology had a more favorable prognosis than those with diffuse histology (median relapse-free survival of 24 vs. 12 months). There were 2 cases of erythroleukemia, which occurred after combination chemotherapy was given for relapse. Though TBI can offer complete remission and extended survival in advanced NHL, most patients eventually relapse and it should not be considered as a curative mode of therapy.

Blood Cell Count↗
PubMed1979

An evaluation of total nodal irradiation as treatment for stage III A Hodgkin's disease.

Between April 1969 and December 1974, 37 patients with surgically staged III A Hodgkin's disease were treated with total nodal irradiation (TNI). Their probability of relapse-free survival at 7 years is 51% and overall survival 82% with the majority of patients remaining disease free after retreatment with MOPP (10 of 16). In contrast, 21 stage III B patients treated with TNI and MOPP chemotherapy over the same time period have a relapse-free survival of 74% and overall survival of 91%. Because of superior results in treating stage III B patients with combined modality treatment, we fell that a relapse-free survival of 51% may not justify continuation of TNI as the only modality of treatment for patients with stage III A disease, and we have initiated a trial of combined radiation therapy and MOPP chemotherapy in these patients. The most effective treatment of stage III A Hodgkin's disease, however, remains uncertain and depends both on the ultimate risk of combined modality treatment and the success of retreatment following relapse after radiation.

Adolescent↗
PubMed1978

The significance of mediastinal involvement in early stage Hodgkin's disease.

Between April 1969, and December 1974, 111 consecutive surgically staged I A and II A patients with supradiaphragmatic Hodgkin's disease were treated at the Joint Center for Radiation Therapy. Patients received 3600--4400 rad to mantle and para-aortic--splenic pedicle regions. Median follow-up was 56 months (30--96). Fourteen patients developed relapsing Hodgkin's disease and three patients died of possible treatment-related causes, two with acute myocardial infarctions and one with radiation pneumonitis. Patients with mediastinal enlargement greater than one third of the chest diameter have a significantly higher risk (p less than 0.01) of developing relapse (9 of 18) than patients with lesser or no mediastinal disease (5 of 93). Of the 18 patients with large mediastinal disease, six relapsed in the mediastinum and two in the lung. There continue to be no pelvic extensions in the entire group. There is a 92% relapse-free and 97% overall survival in the 93 patients without extensive mediastinal disease. We continue to recommend mantle and para-aortic--splenic pedicle irradiation for these patients. In view of the large number of relapses in patients with extensive mediastinal disease, we are now treating this subgroup of patients with MOPP chemotherapy in addition to mantle and para-aortic irradiation.

Adolescent↗